PE-22-28
Also known as: Spadin analog, TREK-1 blocker peptide, GVSWGLR
PE-22-28 (also called Spadin analog or TREK-1 blocker peptide) is a TREK-1 research peptide in the Neuromodulator class. PE-22-28 is a shortened analog of spadin, a peptide derived from the propeptide released when sortilin is matured. It blocks TREK-1, a two-pore-domain potassium channel encoded by KCNK2.
For research use only.
Key Facts
- CAS
- 1801959-12-5
- Molecular Weight (MW)
- 773.9 g/mol
- Half-life
- —
- FDA status
- Not Approved
- Administration Route
- Subcutaneous
- Frequency
- Research-dependent
- Last updated
- Aug 30, 2026
- Reviewed
- Aug 30, 2026
- Targets
- TREK-1 (KCNK2)
Research summary
Shortened analog of spadin, a peptide derived from sortilin maturation, which blocks the TREK-1 potassium channel. Because mice lacking TREK-1 show a depression-resistant phenotype, the channel became an antidepressant target, and PE-22-28 produces antidepressant-like effects in rodents within days rather than the weeks required by monoamine reuptake inhibitors. Preclinical only, with no human trials, and not FDA-approved.
Peptide Library's PE-22-28 profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.
Protocol
- Dosage Range
- Per published research protocol — not a clinical label
- Frequency
- Research-dependent
- Cycle
- —
- Administration Route
- Subcutaneous
- Reconstitution Guide
- —
- Injection Sites
- AbdomenThigh
- Timing Notes
- Educational catalog only — not medical advice
Sequence & molecular data
| Amino acid sequence | GVSWGLR |
|---|---|
| Molecular formula | C35H55N11O9 |
| Molecular weight | 773.9 g/mol |
| CAS number | 1801959-12-5 |
| Appearance | White lyophilized powder |
| Formulation | Lyophilized Powder |
Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.
Science
Mechanism of Action
PE-22-28 is a shortened analog of spadin, a peptide derived from the propeptide released when sortilin is matured. It blocks TREK-1, a two-pore-domain potassium channel encoded by KCNK2. TREK-1 activity hyperpolarises neurons and dampens excitability, and mice lacking the channel show a depression-resistant phenotype, which is what made it a target. Blocking TREK-1 increases excitability of serotonergic neurons in the dorsal raphe and promotes hippocampal neurogenesis, producing antidepressant-like effects in rodents within days rather than the weeks required by monoamine reuptake inhibitors. The evidence is preclinical; no human trials have been published.
Origin
Synthetic GVSWGLR analog of spadin.
Targets
Studies
- Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity
- Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin
- The Involvement of Sortilin/NTSR3 in Depression as the Progenitor of Spadin and Its Role in the Membrane Expression of TREK-1
- Spadin as a new antidepressant: absence of TREK-1-related side effects (class-level evidence)
- Spadin Selectively Antagonizes Arachidonic Acid Activation of TREK-1 Channels (class-level evidence)
Regulatory & research status
PE-22-28 is not an FDA-approved product. It is sold for laboratory research and has no approved medical use.
| FDA status | Not Approved |
|---|---|
| Availability | Research-Only |
| WADA (sport) | Unknown / Not Listed |
| Library classification | Research-Only |
Benefits
Potential Side Effects
Side Effects
- No established human AE profile
Storage & stability
Lyophilized (freeze-dried) peptide powder is far more stable than the reconstituted solution. Keep sealed vials cold, dry and away from light; long-term storage is typically frozen, with short-term refrigeration for vials in use.
Once reconstituted in bacteriostatic water, keep the solution refrigerated, avoid repeated freeze–thaw cycles and agitation, and label the vial with the reconstitution date and concentration. Discard any solution that turns cloudy or shows particulates.
Degradation rates differ by sequence: peptides containing methionine, cysteine, asparagine or glutamine are more prone to oxidation and deamidation, so shelf life after reconstitution is compound-specific rather than universal.
Read the full guide: how to store peptides before and after reconstitution →
Source: Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm Res. 2010;27(4):544–575. (PMID 20143256). General guidance for research handling; not product-specific instructions.
PE-22-28: frequently asked questions
What is PE-22-28?
Shortened analog of spadin, a peptide derived from sortilin maturation, which blocks the TREK-1 potassium channel. Because mice lacking TREK-1 show a depression-resistant phenotype, the channel became an antidepressant target, and PE-22-28 produces antidepressant-like effects in rodents within days rather than the weeks required by monoamine reuptake inhibitors. Preclinical only, with no human trials, and not FDA-approved.
How does PE-22-28 work?
PE-22-28 is a shortened analog of spadin, a peptide derived from the propeptide released when sortilin is matured. It blocks TREK-1, a two-pore-domain potassium channel encoded by KCNK2.
Is PE-22-28 FDA approved?
No. PE-22-28 is not approved by the FDA for any indication and is categorised as research-only. It has not been reviewed for safety or efficacy as a medicine, and published research should be read as investigation rather than established use.
What is the amino acid sequence of PE-22-28?
PE-22-28 has the sequence GVSWGLR. Its molecular formula is C35H55N11O9.
What peptides are similar to PE-22-28?
Compounds most often compared with PE-22-28 include Delta Sleep-Inducing Peptide (DSIP), N-Acetyl Selank Amidate, Noopept and Orexin-A. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.
References
- Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity — Front Pharmacol, 2017External reference
- Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin — Pharmacol Ther, 2019External reference
- The Involvement of Sortilin/NTSR3 in Depression as the Progenitor of Spadin and Its Role in the Membrane Expression of TREK-1 — Front Pharmacol, 2018External reference
- Class-level evidence — Spadin as a new antidepressant: absence of TREK-1-related side effects — Neuropharmacology, 2012External reference
- Class-level evidence — Spadin Selectively Antagonizes Arachidonic Acid Activation of TREK-1 Channels — Front Pharmacol, 2020External reference
Related research, comparisons & guides
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Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Aug 30, 2026 · Version 1
This PE-22-28 profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error
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